Chondroprotective effects of Salubrinal in a mouse model of osteoarthritis.

OBJECTIVES: Salubrinal is a synthetic agent that elevates phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α) and alleviates stress to the endoplasmic reticulum. Previously, we reported that in chondrocytes, Salubrinal attenuates expression and activity of matrix metalloproteinase 13 (MMP13) through downregulating nuclear factor kappa B (NFκB) signalling. We herein examine whether Salubrinal prevents the degradation of articular cartilage in a mouse model of osteoarthritis (OA). METHODS: OA was surgically induced in the left knee of female mice. Animal groups included age-matched sham control, OA placebo, and OA treated with Salubrinal or Guanabenz. Three weeks after the induction of OA, immunoblotting was performed for NFκB p65 and p-NFκB p65. At three and six weeks, the femora and tibiae were isolated and the sagittal sections were stained with Safranin O. RESULTS: Salubrinal suppressed the progression of OA by downregulating p-NFκB p65 and MMP13. Although Guanabenz elevates the phosphorylation level of eIF2α, it did not suppress the progression of OA. CONCLUSIONS: Administration of Salubrinal has chondroprotective effects in arthritic joints. Salubrinal can be considered as a potential therapeutic agent for alleviating symptoms of OA. Cite this article: Bone Joint Res 2015;4:84-92.

The effect of butyric acid on adhesion molecule expression by human gingival epithelial cells.

BACKGROUND AND OBJECTIVE: Short-chain fatty acids, such as butyric acid, are detected in periodontal pockets and are thought to be involved in the initiation and progression of periodontal disease. In the present study, we examined the effects of butyric acid on adhesion molecule expression by human gingival epithelial cells. MATERIAL AND METHODS: The human gingival carcinoma cell line, Ca9-22, was cultured in media that contained different concentrations of butyric acid. RESULTS: Cell numbers were significantly decreased in a dose-dependent manner by butyric acid at concentrations of > or = 0.2 mM. The expression of intercellular adhesion molecule-1 mRNA was significantly increased 6 h after stimulation. By contrast, the expression levels of integrins alpha 6 and beta 4 were decreased. Similar results were obtained by flow cytometry. CONCLUSION: The results of the present study indicate that butyric acid alters the expression of adhesion molecules by Ca9-22 cells. The elucidation of the mechanism of action of butyric acid on the periodontium may help to clarify several aspects of the onset and progression of periodontal disease.

Factors affecting the digestibility of raw and gelatinized potato starches.

The enzymatic digestibilities of raw and gelatinized starches in various potato starches, as well as sweet potato, cassava, and yam starches, were estimated, along with other starch properties, such as the phosphorus content, median granule size, and rapid visco analyzer (RVA) pasting properties. Furthermore, correlation coefficients were calculated between the hydrolysis rates (HR) by amylase and other starch quality parameters. A larger granule size was closely associated with a lower HR in raw starch, while the HR in gelatinized starch did not correlate with the median granule size. An increase in phosphorus content resulted in a definitely lower HR in raw starch and tended to decrease the HR in gelatinized starch for the composite of potato and other starches. In contrast, no correlation coefficients of the phosphorus content with the HRs in raw and gelatinized starches were observed within potato starches. Starches with higher peak viscosity and breakdown showed a lower HR in raw starch, while few or no effects of these RVA parameters on the HR in gelatinized starch were observed for the composite of potato and other starches or among potato starches, respectively.

Wavelength stabilization of a distributed Bragg reflector laser diode by use of complementary current injection.

We have demonstrated wavelength stabilization in an 821-nm AlGaAs three-section tunable distributed Bragg reflector (DBR) semiconductor laser diode (LD) that consists of active, phase-controlled, and DBR regions. We injected two separate, complementary currents into the active and the phase-controlled regions in the DBR-LD to suppress wavelength shift. This modulation method was applied to the LD fundamental wave in a second-harmonic-generation (SHG) laser, and the oscillating wavelength was maintained within the phase-matching acceptance range of the SHG device during modulation. A peak blue-violet light power of 62 mW was obtained for the ideal modulation waveform.

Novel patterns of amino acid mutations in the hepatitis B virus polymerase in association with resistance to lamivudine therapy in japanese patients with chronic hepatitis B.

Lamivudine is effective in suppressing replication of hepatitis B virus (HBV). However, the emergence of HBV variants resistant to lamivudine is a concern. Lamivudine resistance has been attributed mainly to a substitution of isoleucine or valine for methionine at residue 550 (M550I or M550V) in the catalytic site of the virus polymerase. A substitution of methionine for leucine at residue 526 (L526M) has also been identified. To examine such virus genotypic mutations in Japanese patients, we studied five patients with chronic hepatitis B, who showed HBV breakthrough while on a 1-year lamivudine treatment. The entire nucleotide and deduced amino acid sequences of the proposed reverse transcriptase domain of the polymerase gene were determined on HBV DNA amplified by polymerase chain reaction from patient sera collected at the start and at the end of therapy. The HBV sequences from all five patients were of genotype C. In four patients, a substitution of valine or isoleucine for leucine at residue 426, which has not been reported previously, emerged in combination with M550I. One also harbored L526M. In the remaining patient, an alteration of leucine to methionine at residue 428 co-occurred with M550V. Longitudinal study of the mutations showed that the two or three mutations in each patient emerged almost simultaneously 4 weeks before or at the time of breakthrough and were replaced by wild-type virus after completing the therapy. Our results indicate that occurrence of HBV polymerase mutations at residue 426 in combination with M550I is frequent in Japanese or genotype C virus-in- fected patients who develop resistance to lamivudine.

Drug-induced hypotension SEP test and acetazolamide test using 133Xe SPECT in patients with occlusive carotid disease--selection of candidates for extracranial-intracranial bypass.

The correlation between the drug-induced hypotension somatosensory evoked potential (SEP) test and regional cerebral blood flow changes after acetazolamide administration was studied. Fourteen patients presenting with transient ischemic attack, reversible ischemic neurological deficits, or minor completed stroke were evaluated. All patients had no or only localized low-density areas on computed tomographic scans, and unilateral occlusion or severe stenosis of the internal carotid or middle cerebral artery on cerebral angiograms. The Diamox asymmetry enhancement (DAE) was studied to detect reduced cerebral perfusion reserve in the affected hemispheres. The DAE was 7.9 +/- 5.8% in seven patients positive in the SEP test, significantly higher than -1.5 +/- 2.9% in patients negative in the SEP test. Postoperative SEP tests were negative in all five patients who underwent extracranial-intracranial (EC-IC) bypass surgery, suggesting that the EC-IC bypass improved the cerebral perfusion reserve in the affected hemispheres. The DAE decreased significantly in four of these patients. This study disclosed a significant correlation between the drug-induced hypotension SEP test and DAE. These parameters are considered important for evaluating patients with hemodynamic compromise and/or suitable candidates for EC-IC bypass.

[Diagnosis of hemodynamic compromise in patients with chronic cerebral ischemia; measurement of cerebral blood volume (CBV) with 99mTc-RBC SPECT].

To evaluate the efficacy of tests for selecting patients with hemodynamic compromise, measurement of cerebral blood volume (CBV) with 99mTc-RBC single photon emission computed tomography (SPECT) was performed in thirteen patients with occlusive cerebrovascular disease, and was compared with results obtained by 133Xe SPECT and acetazolamide (Diamox) test. All patients in our study suffered TIA, RIND, or minor complete stroke. Cerebral angiography demonstrated severe stenosis or occlusion in the ipsilateral internal carotid artery or middle cerebral artery, although plain CT scan or MRI revealed no or, if any, only localized infarcted lesions. Regional cerebral blood volume (rCBV) was measured with 99mTc-RBC SPECT and regional cerebral blood flow (rCBF) was measured with 133Xe SPECT before and after intravenous injection of 10 - 12 mg/kg acetazolamide (Diamox). Our results suggest that the ipsilateral rCBV/rCBF (mean transit time) is a more sensitive index of the cerebral perfusion reserve than the use of only rCBV or rCBF of the ipsilateral hemisphere. Also, the ipsilateral rCBV/rCBF is significantly correlated (r = -0.72) with the Diamox reactivity of rCBF, which is considered to represent the cerebral vasodilatory capacity in patients with chronic cerebral ischemia. Postoperative SPECT study revealed remarkable improvement of ipsilateral rCBV/rCBF and Diamox reactivity in four patients who underwent EC/IC bypass surgery to improve the hemodynamic compromise. In conclusion, our results suggest that the measurement of rCBV/rCBF with 133Xe SPECT and 99mTc-RBC SPECT is useful for detecting the hemodynamic compromise in patients with occlusive cerebrovascular disease.

[Diagnosis of hemodynamic compromise in patients with chronic cerebral ischemia; the detection of impaired vasodilatory capacity with 133Xe SPECT and acetazolamide (Diamox) test].

To evaluate the efficacy of 133Xe SPECT and Diamox test, for selecting patients with hemodynamic compromise, tests using 133Xe inhalation method and single photon emission computed tomography (SPECT) with acetazolamide (Diamox) were performed in twenty-three patients with chronic cerebral ischemia, before and after extracranial-intracranial bypass surgery or carotid-endarterectomy. All patients complained of TIA, RIND, or minor completed stroke, and cerebral angiography of all patients demonstrated severe stenosis or occlusion in the ipsilateral internal carotid artery or middle cerebral artery. Cerebral blood flow (CBF) was also measured 15 minutes after intravenous administration of 10-12 mg/kg Diamox, which is known as a cerebral vasodilatory agent (Diamox test). Our results revealed that all patients could be divided into four types according to the findings of their resting rCBF and Diamox reactivity. The patients who had normal resting rCBF and normal Diamox reactivity (type 1) were considered to have well-developed collateral circulation and normal cerebral perfusion pressure (CPP) in spite of severe occlusive lesions in the carotid system. Moderate vasodilatation due to reduced CPP was considered to occur in patients who had normal resting rCBF and decreased Diamox reactivity (type 2). The resting rCBF remained unchanged, but Diamox reactivity improved to the normal range after surgery in the patients of type 2 (p less than 0.01), which indicated the improvement of CPP and the resolution of the autoregulatory vasodilatation. Maximum vasodilatation or dysautoregulation was considered to occur due to the inadequate collateral flow and the severely reduced CPP in patients whose findings revealed decrease in the resting rCBF and impaired Diamox reactivity (type 3).(ABSTRACT TRUNCATED AT 250 WORDS)